Process for the preparation of 2-oximino-6-nitro hexanamide

ABSTRACT

2-OXIMINO-6-NITRO HEXANAMIDE IS SUITABLY PURIFIED BY RECRYSTALLIZATION FROM A SOLVENT SELECTED FROM THE GROUP CONSISTING OF (A) C1 to C3 dialkyl ethers of ethylene glycol, and (b) C2 to C5 halogenated alkanes having a Cl/C atom ratio ranging from about 1:1 to 1:3.

United States Patent 1 Fuhrmann et al.

[451 May 8, 1973 PROCESS FOR THE PREPARATION OF 2-OXIMINO-6-NITRO HEXANAMIDE Inventors: Robert F ihrmann, Morris Plains; Fred W. Koff, Clifton; John Pisanchyn, Morristown, all of NJ.

Assignee: Allied Chemical Corporation, New

York, NY.

Filed: Oct. 14, 1971 Appl. No.: 189,365

US. Cl. ..260/56l A ..C07c 103/00 Field of Search ..260/561 A Primary ExaminerLewis Got ts Assistant ExaminerEthel G. Love AttorneyvArthur J. Plantamura et a1.

57 ABSTRACT 2-oximino-6-nitro hexanamide is suitably purified by recrystallization from a solvent selected from the group consisting of (a) C to C dialkyl ethers of ethylene glycol, and (b) C to C halogenated alkanes having a Cl/C atom ratio ranging from about 1:1 to

2 Claims, No Drawings nag PROCESS FOR THE PREPARATION OF 2- OXIMINO--NITRO HEXANAMIDE CROSS-REFERENCE TO RELATED APPLICATIONS This application is related to copending, commonly assigned applications Ser. No. 097,290 filed D'ec. ll, 1970, and Ser. Nos. 852,947 now U.S. Pat. No. 3,681,460, and 852,881, now abandoned, both filed August 25, 1969.

BACKGROUND OF THE INVENTION compound III to avoid poisoning of the catalyst and also formation of side products which are extremely difiicult to remove from compound III. Needless to say, any compound intended for ingestion by humans or animals must be scrupulously free of contaminating side products. Y

It should be noted that purification of compound I by methods other than recrystalliz 'ation" is either not economically feasibleor inoperable. Compound I, for example, is not sufficiently thermally stable to withstand distillation or sublimation. As heretofore indicated, the priorlart t'eaches the purification of compound I by recrystallization from water. We have found that water possesses serious shortcomings as a recrystallization solvent. Specifically, we have found that the subsequent catalytic reduction of compound I to afford compound Ill must be carried out under scrupulously anhydrous conditions to avoid a substantial loss in product yield through cleavage of the C=NOH group. If compound I is recrystallized from water, a

small amount thereof will invariably occluded in the HON -NO2 0 ii CHg(CH1)3C NH:

N02 NOH (Lysine amide (III) German Offenlegunsschrift Pat. No. 1,926,857 also teaches the preparation of compound III above by a similar route. Purification of said compound I by recrystallization from water is also taught therein. We

have, however, found that recrystallization of com pound I from water or other conventional recrystallization solvents possesses numerous disadvantages not encountered when recrystallization is effected from certain specific solvents utilized in accordance with the-instant invention.

SUMMARY OF THE INVENTION It has now been found in accordance with the instant invention that recrystallization of 2-oximino6-nitro hexanamide (compound I) from a solvent selected from the group consisting of C to C dialkyl ethers of ethylene glycol and C, to C halogenated alkanes having a Cl/C atom ratio ranging from about 1:1 to about 1:3 is superior to other known methods of purification.

Purification of compound I by some method is essential prior to the catalytic reduction thereof to afford recovered crystals. This occluded water must be removed by thorough drying, usually at. reduced pressure, if the aforementioned loss of product on hydrogenation is to be avoided. In contradistinction, the solvents of the instant invention are not significantly occluded by the crystals and additionally, any that is occluded has no significant adverse effect on the subsequent hydrogenation. 7

Most other non-aqueou s recrystallization solvents are ineffective for either orboth of the two following reasons: 7 v

l. The recovered crystals still contain a significant amount of side products and contaminants, i.e., the

'side product and/or contaminants do not remain dissolved in the recrystallization solvent mother liquor.

2. The recovery of purified product from the solvent is unduly low. At least about percent of the compound I dissolved in the solvent should be recovered as pure crystals to avoid excessive loss of product yield. Only the solventsenumerated herein have been found ing of C to C dialkyl ethers of ethylene glycol and C, .to C halogenated alkanes having a Cl/C atom ratio ranging from about 1:1 to about 1:3.

The actual recrystallization procedure utilized is conventional in the art. That is, one part of crude recovered compound I is dissolved in from about 1 to 50 or more parts by weight of solvent, preferably with agitation and heating. The solution is then cooled to a temperature ranging from slightly above room temperature, down to about C., and let stand until crystals of the pure compound I form. If desired, crystallization can be encouraged by seeding. These crystals are then recovered by filtration, decantation or other known methods. Preferably, dissolution is effected in about to 30 parts by weight of solvent heated at or almost at reflux, followed by slow cooling to about OC. to .efi'ect crystallization. The exact amount of solvent chosen and temperature of heating 5 for solution and of cooling for crystallization can, of course, be readily determined by routine experimentation. The solvents of the instant invention are uniquely superior in that a very high recovery 90 percent) of the desired product is obtained while essentially all of the contaminants remain dissolved in the solvent. All other solvents tried from which recrystallization was even possible gave eithersignificantly lower recovery of crystals or the crystals contained occluded impurities, or both. I g Illustrative of the solvents of the instant invention are glyme (ethylene glycol dimethyl ether), l-methoxy-Z- ethoxy ethane, ethylene glycol diethyl'ether, 1,2-di-npropoxy ethane, l ,2-dichloroethane, 2,2- dichloroethane, 2,3-dichloropropane, 1,3- dichloropropane, 'l,4-dichlorobutane, 2,2,3-

trichlorobutane l,2,3,4,5-pentachloropentane. Mixtures of any of the solvents of the instant invention nificant advantage over the use of a single solvent.

EXAMPLE 200 parts of a-nitrocycloheianone was reacted with nitrosyl'chloride using SO, as'a reaction solvent to afford 2-nitro-6-oximinocyclohexanone. The reaction mixture was stripped and the' residue (195 parts) dissolved. in anhydrous ammonia (200 parts) containing 400 parts of anhydrous methanol in a glass' 'lined preswas used to supply aliquots for testing various recrystallization solvents. In each case, 5 parts of crude product were dissolved in 40 parts of solvent heated to the boiling point. The solution was then allowed'to cool slowly to ambient temperature. If no crystals formed after l2- hours standing at ambient temperature, the solution was cooled to 0 for 24 hours. If still no crystal formation occurred, then the solution was evaporated down to a total weight of 20 parts and cooled again, first to ambient temperature and then to 0C. as before. In no case where no crystallization occurred with 40 parts of solvent did further reduction in volume afford crystals. Results are tabulated below. r

Recrystallized Product Solvent Product Melting Point,'C

. Yield,

glyme 90 96.5 97.5

l-methoxy-2-ethoxy- 92 97 97.5 ethane ethylene glycol 90 96.5 97.5 diethylether (diglyme) l,2-di-n-propoxy 93 96 97 ethane l ,Z-dichloroethane 9 l 98 2,2-dichloroethane 94 97 97.5 l,3-dichloropropane 90 96 97 l,2-dichloropropane 97 96 97 1,4-dichlorobu'tane 93 96 97 l,2,3,4,5-pentachloro 92 96 97 pentane methanol 0 ethanol 0 CC! (insoluble) 0 CHCI, (insoluble) 0 acetone 0 benzene 5O 90 95 toluene 60 90 95 water 0 /50 water ethanol 65 91 95 methyl ethyl ketone O acetonitrile 0 isopmpanol 0 nitromethane 0 nitroethane 0 dioxane 0 tetrahydrofuran 0 butyl acetate 0 The recrystallized product (2 oximino 6 -riitrohexana- 'mide) has a melting point of about 97.5C. and in all cases,-the structure of isolated product was checked by LR. and NMR spectrographic analysis. The product tane, cyclohexane and diisopropyl ether. 7

I canb e-utilized for recrystallization, but provide no sig- 1. In a process comprising nitrosating Z-nitrocyclohexanone to afford 2-nitro-6-oximinocyclohexanone, ammoniating said 2-nitro-6-oximinocyclohexanone to afford 2-oximino-6-nitrohexanamide and then reducing sure've sselwhich was then se'a'led andsha'ken for one hour at 80 C. The vessel was then cooled to ambient temperature, vented and the ammonia and-methanol stripped off. The residue of crude product v(r200 parts) said' 2-oximino-6-nitro-hexanamide to afford lysine amide, the improvement comprising purifying said 2- oximino-6-nitrohexanamide prior to said reduction by recrystallization from a solvent selected from the group consisting of C to C dialkyl ethers of ethylene glycol and C, to C; halogenated alkanes having a CI to C atom ratio ranging from about 1:! to about 1:3.

2. A process in accordance with claim 1 wherein said 2-oximino-6-nitrohexanamide is recrystallized from 5 j 

2. A process in accordance with claim 1 wherein said 2-oximino-6-nitrohexanamide is recrystallized from 5 to 30 parts by weight of said solvent. 